Replies to post #117470 on Biotech Values

[jq1234]

Ten patients got the two drugs together with interferon and generic ribavirin. All showed no sign of the virus 12 weeks after the treatment was over. One patient had signs of virus at 24 weeks and was again virus-free in another follow-up test 35 days later.

Of 11 patients who took the Bristol-Myers combination alone, five had cleared the virus from their bodies at the end of treatment. Four remained virus-free after 24 weeks.

Without interferon and ribavirin, it doesn't seem BMS-790052 and BMS-650032 combo worked that great.

[genisi]

We've talked about the hight viral breakthrough in group A (BMS-790052 + BMS-650032) of that trial and AE were also kind of hight although generally not so much in group A (except for ALT elevations).

http://www.natap.org/2011/EASL/EASL_28.htm

[genisi]

BMY's interferon/riba sparing combo looks much better in GT1b nulls (no breakthrough like we've seen before):

From AASLD 2011 Annual Meeting

Dual Oral Combination Therapy with the NS5A Inhibitor BMS-790052 and the NS3 Protease Inhibitor BMS-650032 Achieved 90% Sustained Virologic Response (SVR12) in HCV Genotype 1b-Infected Null Responders

Chayama et. al.

Background:
Retreatment of patients with chronic HCV infection and prior null response to peginterferon and ribavirin (P/R) with P/R alone or P/R + telaprevir or boceprevir has limited efficacy. Increasing antiviral activity with 2 potent direct-acting antivirals may achieve SVR without P/R in some patients (Lok et al, EASL 2011). The combination of BMS-790052, a first-in-class NS5A replication complex inhibitor with picomolar potency and broad genotypic coverage in vitro, and BMS-650032, a potent inhibitor of NS3 protease with activity vs genotypes 1 and 4 in vitro, was assessed in Japanese null responders.
Methods:
This ongoing open-label study began with a sentinel cohort of 10 patients with chronic HCV genotype 1 infection and prior null response (<2 log10 reduction in HCV RNA after 12 weeks) to P/R. Patients received BMS-790052 (60mg QD) and BMS-650032 (initially 600mg BID, subsequently reduced to 200mg BID) for 24 weeks. The primary endpoint was undetectable HCV RNA 12 weeks post-treatment (SVR12).
Results:
The 10 enrolled patients were all HCV genotype 1b with median baseline HCV RNA of 6.8 log10 IU/mL and median age of 62 years. Nine patients completed 24 weeks of treatment; 1 patient discontinued after 2 weeks. In all 9 patients who completed treatment, HCV RNA was undetectable from treatment week 8 through post-treatment week 12 (SVR12). In the patient who discontinued, HCV RNA remained undetectable for >24 weeks after discontinuation. There was no viral breakthrough. Polymorphisms associated with resistance to BMS-790052 (L28M, R30Q, L31M, Y93H) and some NS3 protease inhibitors (T54S, Q80L) were detected at baseline in several patients (1 patient had both NS3 and NS5A substitutions) but had no apparent effect on virologic outcomes. Grade 1 diarrhea and headache were the most common adverse events (AE); 3 patients had grade 1/2 transaminase elevations. The 2 serious AEs were hyperbilirubinemia, possibly related to treatments (ie meropenem) for infectious gastroenteritis that led to discontinuation, and pyrexia.
Conclusions:
Oral combination therapy with BMS-790052 and BMS-650032, without P/R, can achieve rapid and durable viral suppression in null responders with HCV genotype 1b infection. 9/10 subjects completed 24 weeks and achieved SVR12; HCV RNA was undetectable after treatment or discontinuation in all 10 patients. The treatment regimen was safe and well-tolerated.

	                                      Week 4 (RVR)	Week 12 (cEVR)	Week 24 (EOT)	SVR12 
 Patients with HCV RNA undetectable, n/N (%)	4/10 (40%)	9/10 (90%)	9/10 (90%)	9/10 (90%)